Although anxiety is hypothesized as a factor in the initiation of abuse and risk for relapse, the molecular mechanisms underlying anxiety, ethanol addiction, and their correlation is not well understood. The recent approach of combining expression profiling with genetic marker mapping has shown great promise in identifying genes affecting complex traits. Therefore, we plan to identify ethanol-induced anxiolysis behavioral quantitative trait loci (QTL) using the BXD recombinant inbred panel and profile brain expression patterns across theBXD lines using Affymetrix oligonucleotide microarrays and identify expression QTLs. By superimposing eQTL results and behavioral QTL for ethanol-induced anxiolysis, the correlation of genetic loci/polymorphisms controlling select ethanol expression networks and the ethanol-induced anxiolysis phenotype will be identified. This approach will offer an opportunity to elucidate the underlying molecular mechanisms involved in the variance of this complex trait. Since the differences in the anxiolytic-like response of ethanol may alter the liability of ethanol abuse, any insight into this mechanism may have novel implications in the study of ethanol abuse.